ABSTRACT
Background. We characterize the evolution of symptoms in those with selfreported SARS-CoV-2 infections and the likelihood of seeking treatment or medical care during different waves of the pandemic. Methods. The NC-CCRP is a longitudinal observational study of 37,820 participants who completed a daily symptom log from April 2020 through February 2022, during which there were 5,167 self-reported COVID-19 infections. Three variant periods were defined as pre-delta, delta, and omicron, based on the predominant variant in North Carolina. Quasi-Poisson and logistic regression models adjusted for demographics and vaccination were used to assess COVID-19 symptoms and their duration and seeking treatment or hospitalization Results. Cough was the most reported symptom in all waves and increased from 77% pre-delta to 85% during omicron (p=0.001). Sore throat was more common during self-reported infections during omicron (71%), compared with 62% during delta and 54% pre-delta (p< 0.001). The largest change in proportion reporting a symptom was loss of taste or smell which decreased from 55% during pre-delta to 17% during omicron (p< 0.001). Compared with the pre-delta period, delta (incidence risk reduction, IRR 0.86;95% CI 0.79-0.93) and omicron (IRR 0.67;95% CI 0.61-0.73) were associated with lower symptom duration. Participants infected during the delta wave were more likely to seek treatment compared with either pre-delta (odds ratio, OR 1.32 95% CI 1.06-1.64) or omicron (OR 1.42;95% CI 1.21-1.67). Omicron period infections were associated with a lower likelihood of self-reported hospitalization compared with pre-delta (OR 0.26;95% CI 0.10-0.59) or delta (OR 0.26;95% CI 0.11-0.60). Vaccination was associated with a reduced likelihood of hospitalization (OR 0.35;95% CI 0.18-0.70). Proportion and Duration of Symptoms by Variant Wave;Unadjusted by Vaccination Status. Conclusion. Our study indicates evolution in symptom presentation and duration by variant period. The omicron wave was associated with shorter duration and lower severity of illness. Longitudinal tracking of symptomology and severity of a novel pathogen provide insights into the evolution of the pathogen in the community and is vital for public health and clinical response.
ABSTRACT
Background. There remain important gaps in knowledge concerning the effects of SARS-CoV-2 infection or vaccination on the human blood proteome. Methods. The CCRP is a longitudinal surveillance study with information on SARS-CoV-2 infections, vaccinations and associated humoral immune responses in over 37,000 individuals. We selected a sample of blood spots cards (n=510) from serum antibody studies obtained between October 2020 and April 2021 for mass spectrometry proteomics analysis covering 540 unique plasma proteins. We analyzed the quantified protein differences based on dried blood samples obtained before and after infection or vaccination among previously non-infected individuals (immune naive) after adjustment for batch effects, age, sex, or prior diagnosis of cancer, cardiovascular or autoimmune disease, or diabetes. The majority of infected individuals were minimally symptomatic. Differentially expressed proteins were considered significant with an FDR adjusted p-value of < 0.05 and log2 fold change (L2FC) >0.2. Results. We found 11 and 12 proteins differentially expressed proteins in the naive/infected and naive/vaccinated people respectively, of which 10 were shared. Hepatocyte growth factor receptor (HGF) was upregulated (L2FC 0.24;p < 0.001) only in those who were infected while fibrillarin (L2FC -0.24;p< 0.001) and lambdacrystallin homolog (L2FC -0.29, p < 0.001) were downregulated only in the vaccinated samples (Fig 1). The remaining DE protein were associated with a wide array of functions including metabolic, cytostructural, extracellular matrix and DNA regulatory processes. Conclusion. We found changes in the proteome both from infection and vaccination. HGF, elevated in the infected, has been associated with endothelial inflammation, upregulation of pro-inflammatory cytokines to reduce lung fibrosis and is known to promote tissue repair. Fibrillarin, downregulated in the vaccinated, has been associated with higher rates of bacterial and viral clearance, inflammation reduction, and increased cell survival. These findings suggest detectable complex inflammation from mild to moderate infections. Further investigation is required to understand the mechanism of action and clinical implication of these findings.
ABSTRACT
Background. Longitudinal serological surveillance is critical to understand dynamics of SARS-CoV-2 infections in children, a substantial portion of whom are asymptomatic. We describe trends in seroprevalence using at-home testing and evaluate demographic and clinical characteristics associated with seroconversion. Methods. Children 2-17 years old enrolled at 3 North Carolina sites (Figure 1) were followed April 2- December 31, 2021. Daily electronic surveys solicited symptoms and vaccination status. Four fingerprick lateral flow immunoassay tests were shipped to participants to be completed monthly;sensitivity and specificity were 84.5% and 99.0%, respectively. We defined an infection window as 30 days before a positive antibody test (IgG), excluding results after any vaccine. Asymptomatic was defined as absence of "new" symptoms in the window;"new" was defined as not occurring the 14 days preceding the first observation of the symptom in the window. Univariate logistic regression was used to compare participants with and without infection-induced antibodies. For estimated seroprevalence, we used Bayesian inference accounting for sensitivity and specificity, modeling IgG positives from a binomial distribution. Results. Of 1,501 participants, 9.1% developed infection-induced antibody (Table 1). Blacks were more likely to seroconvert (OR 1.95 [95% CI 1.05-3.45]) as were those in a 5-or-more person household (OR 4.25 [CI 1.47-12.1]). Cumulative seroprevalence of SARS-CoV-2 increased from 12.7% in May to 32.4% in October (Figure 2);61% of those seropositive were asymptomatic (Table 2). Adolescents had the highest seroconversion rates and were significantly more likely than 2-4-year olds to be asymptomatic. Conclusion. Prior SARS-CoV-2 seroprevalence data in children are limited by cross sectional design and use of convenience samples. With serial testing, we demonstrate rising SARS-CoV-2 seroprevalence, with highest rates of seroconversion in adolescents. Although prior findings suggest that asymptomatic infections occur most frequently in young children, we found a high proportion among adolescents. Our findings underscore the importance of serosurveillance to optimize public health efforts aimed at children and adolescents. (Table Presented).
ABSTRACT
Background. The COVID-19 Community Research Partnership (CCRP) is a large multicenter healthcare system-based study of the COVID-19 pandemic, including factors impacting risk of infection and hospitalization. The CCRP includes a subset of immunocompromised (IC) participants with varying vaccination status over time. Methods. We conducted an observational cohort study of 2,515 IC and 41,941 non-IC CCRP participants who contributed electronic health record data and daily electronic surveys to self-report COVID-19 symptoms, test results, and vaccinations from April 2020 to March 2022. The IC population included those with stem cell transplant, HIV, cancer, autoimmune disease, or solid organ transplant. The latter 3 must have also had an active systemic therapy to meet the IC condition (e.g. chemotherapy, immune modulator, steroid). Logistic regression was used to investigate risk of COVID-19 and hospitalization among IC participants and according to vaccine status within viral variant time periods (pre-delta, delta, omicron). Results. IC conditions included cancer (51%), autoimmune (41%), solid organ/ stem cell transplant (9%), and HIV (7%). The IC group was older and had more comorbidities. 95% of vaccine recipients received an mRNA vaccine. More vaccine breakthrough infections occurred in the IC group than non-IC group (36.1% vs 29.5%, p< 0.001). IC participants were less likely to remain COVID-19 free over time if vaccinated but not boosted (Fig 1A). However, after receiving a booster there was no difference in COVID-19 cases between the groups (Fig 1B). IC participants were more likely to be hospitalized with COVID-19 (OR 2.85;95% CI 1.69-4.76), but vaccination reduced risk for hospitalization (OR 0.26;95% CI 0.08-0.8). Receipt of a booster dose reduced risk of COVID-19 among IC participants during the delta wave (IRR 0.52;95% CI 0.28-0.94) but not during omicron. However, during omicron risk of hospitalization in the IC group was reduced by a booster dose (OR 0.13;95% CI 0.02-0.72). Conclusion. IC individuals were at increased risk for COVID-19 hospitalizations and breakthrough infections. After receiving a booster, IC participants were conferred the same level of protection from infection as their non-IC counterparts, highlighting the importance of boosters for these individuals. (Figure Presented).